New Steroidal Selenides as Proapoptotic Factors

Cytostatic and pro-apoptotic effects of selenium steroid derivatives against HeLa cells were determined. The highest cytostatic activity was shown by derivative 4 (GI₅₀25.0 µM, almost complete growth inhibition after three days of culture, and over 97% of apoptotic and dead cells at 200 µM). The results of our study (cell number measurements, apoptosis profile, relative expression of apoptosis related APAF1, BID, and mevalonate pathway-involved HMGCR, SQLE, CYP51A1, and PDHB genes, and computational chemistry data) support the hypothesis that tested selenosteroids induce the extrinsic pathway of apoptosis by affecting the cell membrane as cholesterol antimetabolites. An additional mechanism of action is possible through a direct action of derivative 4 to inhibit PDHB expression in a way similar to steroid hormones.

This study was supported by the Ministry of Education and Science, Poland, as a part of subsidies for maintaining the research potential granted to the Faculty of Biology (SWB-8) and Faculty of Chemistry of the University of Białystok. The equipment used for the cell culture at the Laboratory of Tissue Culture was funded by the Ministry of Science and Higher Education (grant no. 8636/E342/R/2014; Restructuration of Faculty of Biology and Chemistry). This work was financed from a scientific project by the subsidy of the Medical University of Bialystok (B.SUB.23.306).

Izabella Jastrzębska: [email protected]

Adam Tylicki: [email protected]

Izabella Jastrzębska - Faculty of Chemistry, University of Białystok

Natalia Wawrusiewicz-Kurylonek - Department of Clinical Genetics, Medical University of Białystok

Paweł A. Grześ - Faculty of Chemistry, University of Białystok

Artur Ratkiewicz - Faculty of Chemistry, University of Białystok

Ewa Grabowska - Doctoral School of Exact and Natural Sciences, University of Bialystok

Magdalena Czerniecka - Faculty of Biology, University of Białystok

Urszula Czyzewska - Faculty of Biology, University of Białystok

Adam Tylicki - Faculty of Biology, University of Białystok

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